Helicobacter pylori lipid A exhibited no or very low endotoxic activities i.e., lethal toxicity in galactosamine-loaded mice, pyrogenicity for rabbits and the activity of the Limulus test when compared with Escherichia coli-type synthetic lipid A (compound 506). The endotoxic properties of H.pylon lipid A were also a little weaker than those of the low endotoxic lipid A of P.gingivalis. The mitogenic activity of H.pylori lipid A in murine splenic mononuclear cells was also less than those of P.gingivalis lipid A and compound 506. On the other hand, H.pylori lipid A induced comparable production of interleukin-6 (IIL-6) by human peripheral blood mononuclear cells (PBMC) as compared with P.gingivalis lipid A and compound 506. H.pylori lipid A also increased definitely human natural killer cell activity, and strongly agglutinated rabbit erythrocytes. However, the lipid As of H.pylori and P.gingivalis showed lower activities in inducing tumor necrosis factor alpha (TNF-alpha) production by
… More human PBMC and IL-8 production by human gingival fibroblasts than that of compound 506. The structural feature of H.pylori lipid A may be associated with low endotoxic properties and potent immunobiological activities. Futher, a systemic infection by Gram-negative bacteria results in septic shock which is mainly caused by macrophages stimulated with endotoxic lipopolysaccharides (LPS). The administration of non-toxic lipid A of P.gingivalis results in lower induction of IL-1beta production and its mRNA expression, whereas the lipid A exhibited higher calmodulin kinase activation in comparison with that of endotoxic synthetic lipid A of E.coli in alveolar macrophages of galactosamine-loaded mice. A calmodulin kinase activator and anti-IL-beta monoclonal antibody also protected mice against endotoxic lipid A-induced lethal toxicity.1) H.pyloriおよびF.gingivalis由来のリピドAによるマウス致死活性,発熱作用,シュワルツマン反応およびリムルステストのいずれの内毒素活性も,大腸菌やサルモネラ属菌タイプのリピドA(化合物506および516)のそれらに比較して非常に低毒性であった.2) H.pyloriリピドAのマイトジェン活性は,供試したいずれの系統の異なるマウス脾細胞に対しても活性がみられなかった.F.gingivalisリピドAでは,BALB/c,C3H/HeNおよびC3H/HeJマウスにおいて明確な活性がみられた.サイトカイン産生性では,H.pyloriおよびF.gingivalisリピドAは,低IL-1β,高IL-6であり,同mRNAレベルにおいても同様な所見が得られた.また,多クローン性B細胞活性化作用,アジュバント作用,非特異的・特異的感染防御作用,ナチュラルキラー細胞活性や特異的腫瘍免疫増強作用は,化合物506および516のそれらと同程度の活性がみられ,低毒性でかつ有用な免疫薬理学的活性を発揮することがわかった.3) ガラクトサミン負荷マウス由来の肺胞マクロファージからのサイトカイン産生は,カルモデュリン(CaM)阻害剤により特異的に抑制された.4) CaM活性化剤や抗IL-1β抗体により,化合物506によるマウス致死活性を抑制する効果がみられた. Less